The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network

Publication Date


Document Type



Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology


A major function of ubiquitylation is to deliver target proteins to the proteasome for degradation. In the apoptotic pathway in Drosophila, the inhibitor of apoptosis protein 1 (Diap1) regulates the activity of the initiator caspase Dronc (death regulator Nedd2-like caspase; caspase-9 ortholog) by ubiquitylation, supposedly targeting Dronc for degradation by the proteasome. Using a genetic approach, we show that Dronc protein fails to accumulate in epithelial cells with impaired proteasome function suggesting that it is not degraded by the proteasome, contrary to the expectation. Similarly, decreased autophagy, an alternative catabolic pathway, does not result in increased Dronc protein levels. However, combined impairment of the proteasome and autophagy triggers accumulation of Dronc protein levels suggesting that autophagy compensates for the loss of the proteasome with respect to Dronc turnover. Consistently, we show that loss of the proteasome enhances endogenous autophagy in epithelial cells. We propose that enhanced autophagy degrades Dronc if proteasome function is impaired.

DOI of Published Version



Cell Death Differ. 2016 Sep 1;23(9):1555-64. doi: 10.1038/cdd.2016.40. Epub 2016 Apr 22. Link to article on publisher's site

Journal/Book/Conference Title

Cell death and differentiation

Related Resources

Link to Article in PubMed

PubMed ID